In 2002, Collins spent the majority of the season as a reserve linebacker. He played in all thirteen games of the season, making his first two starts in the final two games of the season at the strong safety position. Collins finished the season with 35 tackles (22 solo), one interception, five defended passes, one fumble recovery and eight kickoff returns for 181 yards. His strongest statistical performance of the season was an eight-tackle game in his first start, against Florida A&M University, on November 23.

Collins became a full-time starter at free safety for the Bethune-Cookman Wildcats in 2003. He started 11 of the season's 12 games, missing only a November 15 contest against Howard University. Collins had a breakout season in 2003, leading the Mid-Eastern Athletic Conference in interceptions with six and finished third in the conference in passes defended with 13. He also contributed 54 tackles (33 solo), a fumble recovery, and the first defensive touchdown of his college career (intercepting a pass by Norfolk State University quarterback Willie Mitchell and returning it 45 yards for the score). He was an all-conference selection for the season.

As a senior in 2004, Collins was an Associated Press third-team Division 1-AA All-America selection and first-team All-MEAC honors at the free safety position. He once again led the conference with six interceptions, led his team in solo tackles (34) and passes defended (13), and scored the second and final defensive touchdown of his collegiate career. Collins had an interception in each of the first four games of the 2005 season. He had a memorable performance in the final game of his college career, intercepting FAMU quarterback Ben Dougherty at the Bethune-Cookman 8 yard line with only 1:49 left in regulation, sending the game into overtime and to an eventual 58-52 double overtime Bethune-Cookman victory.

Collins entered the NFL on April 23, 2005 when he was selected in the second round (51st pick overall) of the 2005 NFL Draft by the Green Bay Packers. Collins would become only the second Bethune-Cookman player to make the Packers roster. Some draft experts felt that the Packers drafted Collins too high, referring to him as "a developmental prospect who is very athletic but very raw" and questioning his ability to fully grasp an NFL-caliber defense.

Though he was listed as a cornerback in the draft prospect list, Collins competed in Green Bay for the starting free safety job for the 2005 season. Collins would have large shoes to fill on the Packers roster; in 2004, the Packers free safety was Pro Bowl player Darren Sharper. At the beginning of the 2004 offseason, Sharper left the team over contract issues, eventually signing with the Minnesota Vikings and having another Pro Bowl season for 2005.

However, Collins showed the potential and ability that prompted Packers GM Ted Thompson to select him so early in the draft. He quickly became a physical and emotional presence on a defense which showed tremendous improvement after finishing 26th in overall yards allowed during the 2004 season and in spite of the struggles the Packers faced in their first losing season since 1991. Collins recorded his first notable game on October 30, 2005 against the Cincinnati Bengals. Collins had four total tackles and two passes defended, including a crushing blow to star wide receiver Chad Johnson that forced him to drop a pass from quarterback Carson Palmer and a near interception of Palmer that Collins could have returned for a game-changing touchdown.

Collins did record his first interception three weeks later, in a Monday night showdown with the Vikings on November 21. He also recorded a then season-high 11 tackles in the game (eight solo). The interception was an athletic catch which displayed both Collins' physical prowess and his instincts. Collins finished the 2005 season as an unquestioned starter and defensive leader. His total season statistics were 84 tackles (63 solo), one interception, two forced fumbles and seven passes defended.

In 16 games played during the 2006 season, Collins totaled 80 tackles (65 solo), 15 assists, three interceptions and two forced fumbles. Two of his interceptions came during a 26-7 victory over the Chicago Bears on December 31, 2006.

In 2007, Collins started 13 of the Packers games,missing three due to injury. He totaled 46 tackles(40 solo), no interceptions, no forced fumbles and five passes defended.

In 2008, Collins stepped up his game early in the season with five interceptions with three returned for touchdowns along with seven passes defensed in his first nine games of the season when the Packers secondary was depleted with injuries to starting corner Al Harris and strong safety Atari Bigby. Collins ended the season with a career-high seven interceptions, and led the NFL with three pick-sixes and 295 interception return yards. His performance earned him a spot in the 2009 Pro Bowl.[2]

Collins was selected to his second straight Pro Bowl in 2009 behind former Packer Darren Sharper. He started the game for the NFC due to Sharper's participation in Super Bowl XLIV.

On February 6, 2011, in Super Bowl XLV, Collins picked off an underthrown Ben Roethlisberger pass in the first quarter and weaved his way through the Steelers offense, diving into the endzone for a 37-yard touchdown. It gave the Packers a 14-0 lead as they went on to defeat the Steelers, 31-25. Collins finished Super Bowl XLV with one interception returned for a touchdown, four total tackles (all solo), and one pass defended.

On September 18, 2011, in a game against the Carolina Panthers, Collins was carted off the field in a stretcher after sustaining a neck injury while attempting to tackle Panthers running back Jonathan Stewart. Collins spent the night at the hospital and returned to Green Bay the next day, where it was announced that Collins would miss the remainder of the 2011 season.[3] Collins had suffered a herniated disk in his neck, and underwent single-level cervical fusion surgery.[4]

On April 25, 2012, Green Bay decided to release Collins from the team citing concerns about his ability to return to football after suffering such a severe neck injury.[5] On September 28, 2012, Collins' agent, Alan Herman, announced that his neck injury would most likely end his football career.[6] On August 20, 2014, Collins officially announced his retirement from the NFL via Twitter.[1][7]

Collins and his wife Andrea live in Cross City, Florida. While in college, Collins volunteered at elementary schools and at the YMCA in Daytona Beach. He has also been an instructor at a passing camp for children ages 6 to 15. He has a daughter named Jenajah, and two sons, Nicholas Jr. and Nmar'e.[9]